chr16-55464137-G-A

Variant names:

• chr16-55464137-G-A
• rs12924764
• ENST00000570308.5:c.-349-415G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000570308.5(MMP2):​c.-349-415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,066 control chromosomes in the GnomAD database, including 19,591 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (19591 hom., cov: 33)
• Consequence: MMP2 ENST00000570308.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 4 publications found

Genes affected

MMP2 (HGNC:7166): (matrix metallopeptidase 2) This gene is a member of the matrix metalloproteinase (MMP) gene family, that are zinc-dependent enzymes capable of cleaving components of the extracellular matrix and molecules involved in signal transduction. The protein encoded by this gene is a gelatinase A, type IV collagenase, that contains three fibronectin type II repeats in its catalytic site that allow binding of denatured type IV and V collagen and elastin. Unlike most MMP family members, activation of this protein can occur on the cell membrane. This enzyme can be activated extracellularly by proteases, or, intracellulary by its S-glutathiolation with no requirement for proteolytical removal of the pro-domain. This protein is thought to be involved in multiple pathways including roles in the nervous system, endometrial menstrual breakdown, regulation of vascularization, and metastasis. Mutations in this gene have been associated with Winchester syndrome and Nodulosis-Arthropathy-Osteolysis (NAO) syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

MMP2 Gene-Disease associations (from GenCC):

• multicentric osteolysis, nodulosis, and arthropathy

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• multicentric osteolysis-nodulosis-arthropathy spectrum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000570308.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP2	ENST00000570308.5	TSL:1	c.-349-415G>A		intron	N/A	ENSP00000461421.1	P08253-2

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76100 AN: 151946 Hom.: 19561 Cov.: 33

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.483

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.501 AC: 76180 AN: 152066 Hom.: 19591 Cov.: 33 AF XY: 0.506 AC XY: 37595 AN XY: 74322

African (AFR) AF: 0.434 AC: 17993 AN: 41452

American (AMR) AF: 0.609 AC: 9307 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1298 AN: 3470

East Asian (EAS) AF: 0.829 AC: 4271 AN: 5154

South Asian (SAS) AF: 0.525 AC: 2537 AN: 4828

European-Finnish (FIN) AF: 0.524 AC: 5536 AN: 10568

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33883 AN: 67986

Other (OTH) AF: 0.487 AC: 1031 AN: 2116

Alfa AF: 0.501 Hom.: 33364

Bravo AF: 0.507

Asia WGS AF: 0.673 AC: 2337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.72
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12924764; hg19: chr16-55498049;